Study With Wee-1 Inhibitor MK-1775 and Carboplatin to Treat p53 Mutated Refractory and Resistant Ovarian Cancer

• Status: Unknown status
• Trial end date: 2013-09-01
• Target enrollment: 0
• Participant gender: Female

Summary

The purpose of this study is to determine if patients with p53 mutated epithelial ovarian cancer that have been treated with first line treatment (paclitaxel - carboplatin combination therapy) and that have shown early relapse (within 3 months) or progression during treatment will benefit from treatment with Wee-1 inhibitor MK-1775 and carboplatin.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Netherlands Cancer Institute
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Adavosertib; Carboplatin

Criteria

Inclusion Criteria:

• Histological or cytological proof of epithelial ovarian cancer, and proven p53 mutated pathway by PCR/Sequencing. IHC will also be performed.

• Measurable disease on a CT-scan or elevated Cancer Antigen (CA)-125 levels that can be monitored.

• Patients previously received standard 1st line platinum therapy (combined with paclitaxel) for epithelial ovarian cancer, and showed recurrence on or within 3 months of this treatment.

• Able and willing to voluntarily give written informed consent.

• Able and willing to undergo blood sampling for pharmacokinetics and pharmacodynamics.

• Life expectancy ≥ 3 months allowing adequate follow up of toxicity evaluation and anti-tumor activity.

• Minimal acceptable safety laboratory values:

• Absolute neutrophil count (ANC) of ≥ 1.5 x 109 /L (or 1500/m3).

• Platelet count of ≥ 100 x 109 /L (or 100,000/mm3).

• Hemoglobin ≥ 5.6 mmol/L (or 9.1 g/dl).

• Hepatic function as defined by serum bilirubin ≤ 1.5 x ULN, ALAT and ASAT ≤ 2.5 x ULN, or ALAT and ASAT ≥ 5x ULN in case of liver metastases.

• Renal function as defined by serum creatinine ≥ 1.5 x ULN or creatinine clearance ≥ 60 ml/min for patients with creatinine levels ≥ 1.5 x ULN (by Cockcroft-Gault formula).

• WHO performance status of ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

• No radio- or chemotherapy within the last 4 weeks prior to study entry (palliative limited radiation for pain reduction is allowed)

• Able and willing to swallow oral medication.

• Able and willing to receive iv medication.

• Negative pregnancy test (urine/serum) for female patients with childbearing potential.

Exclusion Criteria:

• Symptomatic cerebral or leptomeningeal metastases.

• Current participation or previous participation in a study with an investigational compound, or chemo- and/or radiotherapy within 28 days of receiving first dose of study medication. (Palliative limited radiation for pain reduction is allowed only between day 8 and day 21 of the study, and allowed to a limited area to palliate pain.

• No prior radiation therapy to more than 30% of the bone marrow and patient must have recovered for at least 3 weeks from the hematologic toxicity of prior radiotherapy.

• More than 1 prior cytotoxic chemotherapy regimen.

• Prior stem cell or bone marrow transplant.

• Unresolved (> grade 1) toxicities of previous chemotherapy, excluding alopecia.

• Known hypersensitivity to the components of the combination study therapy or its analogs.

• Patient has had prescription or non-prescription drugs or other products known to be metabolized by CYP3A4, or to inhibit or induce CYP3A4 that cannot be discontinued prior to Day 1 of dosing and withheld throughout the study until 2 days after the last dose of study medication

• Bowel obstructions or motility disorders that may negatively affect oral drug absorption.

• Patients with known alcoholism, drug addiction and/or a history of psychotic disorders who are not suitable for adequate follow up.

• Women who are pregnant or breast feeding.

• Fertile women who do not agree to use a reliable contraceptive method throughout the study.

• Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients.

• Patients with a known history of hepatitis B or C.

• Neurological disease that may render a patient at increased risk for peripheral or central neurotoxicity.

• Clinical history suggestive for Li Fraumeni syndrome.